The identification and characterization of cells are important procedures in biology and medicine. Cells are the basic units of life and are deceptively complicated. Some cells remain attached to an extracellular matrix and thus form part of a larger structure. Other cells are free to move about. Examples of the former are structural cells of green plants and mammalian nerve cells and bone cells. Examples of the latter are bacteria, protozoa, and mammalian blood cells. Some cells are normally attached to extracellular matrices but may be freed by mechanical or enzymatic (proteolytic) disruption and studied, for example cells of the liver (hepatocytes).
Automated liquid flow systems have been used to analyze cells. These systems have found particular application for blood cell analysis in the form of cell counters, hematology analyzers, and flow cytometry systems. Cell counters provide counts of and size of cells in suspension. Hematology analyzers may go further by providing counts on major subsets of white blood cells, such as granulocytes and/or lymphocytes, platelets, and on subsets of red blood cells. Hematology analyzers also measure hemoglobin and additional parameters derived from these basic measured parameters or combinations of these parameters. Flow cytometry systems measure normal and abnormal cells and find application in tracking patients with abnormal cells. Flow cytometers are used in research, and more expensive versions are equipped with cell sorting capability. Flow cytometers are open ended systems requiring significant sample preparation by a trained operator. Hematology analyzers are typically dedicated flow cytometers with automated sample preparation, designed for high volume (large workload) analysis.
One of the disadvantages of flow cytometry systems is that a tiny fraction of cells that are abnormal may not be resolved from a larger population. Another disadvantage is that it is not possible to examine cells after characterization, because the cells have been lost to a waste container. To overcome this latter limitation, cell sorting systems were developed. These flow cytometry systems can direct cells that meet preset criteria to collection containers. These systems, however, are generally very expensive. Moreover, they require a priori knowledge of the cell population characteristics, which is sometimes not available. Another type of cell analysis system has been designed that prepares a blood smear and stains it for each sample so that subsequent microscopic analysis with manual examination is possible. Slide makers and slide stainers can also be separate machines. There are also automated instruments that characterize the images obtained from stained blood smears and other stained smears containing cells. These instruments are sometimes called pattern recognition machines. Generally, pattern recognition systems fail to duplicate the ability of a human technologist to discriminate between normal and abnormal cells and differentiate between different types of cells. Often they are subject to discrimination errors due to variability in staining.
Another disadvantage of flow cytometers and pattern recognition machines is that it is generally difficult and inconvenient to remove the genetic material of cells that have been characterized for further analysis (e.g., sequencing). In addition, flow cytometry systems must generally be periodically cleaned and decontaminated from exposure to hazardous biological materials. Furthermore, when cell populations are measured with automated systems, thresholds must usually be set using calibration standards and controls. Typically, this is achieved with uniformly-sized particles and cell samples that simulate the cells. The calibration procedure requires additional time and is performed on the instrument by a trained operator. Accordingly, flow cytometry instruments are expensive and labor intensive. They are usable by highly trained laboratory professionals, only. Accordingly, there remains a need for a system that can be used for the simple and convenient analysis of cells in solution.